Tamaoka Satoshi, Saito Kazuki, Yoshida Tomoko, Nakabayashi Kazuhiko, Tatsumi Kenichi, Kawamura Toshihiro, Matsuzaki Toshiya, Matsubara Keiko, Ogata-Kawata Hiroko, Hata Kenichiro, Kato-Fukui Yuko, Fukami Maki
Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo Japan.
Department of Perinatal and Maternal Medicine (Ibaraki), Graduate School Tokyo Medical and Dental University Tokyo Japan.
Reprod Med Biol. 2023 Feb 23;22(1):e12504. doi: 10.1002/rmb2.12504. eCollection 2023 Jan-Dec.
Genetic factors associated with the risk of polycystic ovary syndrome (PCOS) remain largely unknown. Here, we conducted an optimal sequence kernel association test (SKAT-O), an exome-based rare variant association study, to clarify whether rare variants in specific genes contribute to the development of PCOS.
SKAT-O was performed using exome data of 44 Japanese patients with PCOS and 301 control women. We analyzed frequencies of rare probably damaging variants in the genome.
Rare variants of were more commonly identified in the patient group than in the control group (6/44 vs. 1/301; Bonferroni-corrected -value, 0.028), while the frequencies of variants in other genes were comparable between the two groups. The identified variants were predicted to affect the function, structure, stability, hydrophobicity, and/or the formation of intrinsically disordered regions of the protein. encodes a glutathione transferase that mediates the oxidative stress response and arsenic metabolism. Previously, common variants in and its paralog were associated with the risk of PCOS.
The results indicate that there are no genes whose rare variants account for a large fraction of the etiology of PCOS, although rare damaging variants in may constitute a risk factor in some cases.
与多囊卵巢综合征（PCOS）风险相关的遗传因素在很大程度上仍不清楚。在此，我们进行了一项最优序列核关联检验（SKAT-O），这是一项基于外显子组的罕见变异关联研究，以阐明特定基因中的罕见变异是否会导致PCOS的发生。
使用44例日本PCOS患者和301例对照女性的外显子组数据进行SKAT-O。我们分析了基因组中罕见的可能有害变异的频率。
患者组中 的罕见变异比对照组更常见（6/44 vs. 1/301；经Bonferroni校正的P值，0.028），而其他基因变异的频率在两组之间相当。所鉴定的 变异预计会影响蛋白质的功能、结构、稳定性、疏水性和/或内在无序区域的形成。 编码一种谷胱甘肽转移酶，介导氧化应激反应和砷代谢。此前， 及其旁系同源基因 中的常见变异与PCOS风险相关。
结果表明，虽然在某些情况下， 中的罕见有害变异可能构成一个风险因素，但没有基因的罕见变异占PCOS病因的很大一部分。
